1. Field of the Invention
This invention relates to mass spectrometry and more specifically to atmospheric pressure ion sources such as Electrospray (ES) and Atmospheric Pressure Chemical Ionization (APCI). The invention includes means for increasing the efficiency of ion transmission from atmospheric pressure into the mass analyzer at high vacuum.
2. Background Art
The Electrospray ionization technique, and more specifically Electrospray ionization sources interfaced to mass spectrometers, have opened a new era of study for the molecular weight determination of labile and involatile biological compounds. The ES technique can produce singly or multiply charged ions in the gas phase from solution at atmospheric pressure. The mass to charge of the ions produced by ES depends on the analyte's molecular weight and solution chemistry conditions. The production of singly and multiply charged ions by electrospray ionization at atmospheric pressure is extensively described by Fenn et al. in U.S. Pat. No. 5,130,538.
Typically, only a small portion of the ions produced at atmospheric pressure can be effectively sampled and transported into high vacuum where they are mass analyzed using a mass spectrometer. For practical and cost reasons, limited pumping speeds are employed in mass spectrometer instrumentation. Consequently, only a limited amount of ion laden atmospheric pressure gas can be "leaked" into vacuum through a small orifice. The gas exiting from a sampling orifice, usually a nozzle or a capillary tube, undergoes a supersonic expansion as it expands into vacuum. As only a limited number of ions produced can be sampled through this orifice into vacuum, it is important to focus as many ions as possible through the region of expanding gas and on into the mass analyzer. The more efficiently the ions are decoupled from the expanding carrier gas and focused into the mass analyzer, the higher is the sensitivity of the overall instrument. Various numbers of pumping stages have been used to remove the gas entering a vacuum system through an orifice from atmospheric pressure and different apparatus and electrostatic lens geometries have been employed to improve the efficiency of ion transmission through specific pumping stage configurations.
Descriptions of ion sources which operate at atmospheric pressure such as ES and APCI interfaced to mass analyzer systems are found in U.S. Pat. Nos. 5,157,260; 5,015,845; 4,999,493; 4,977,320; 4,542,293; 4,531,056; 4,209,696; 4,144,451; 4,137,750; 4,121,099; 4,023,398. In all of these ES and APCI mass spectrometry assemblies, there is a nozzle or a capillary tube orifice communicating between the atmospheric pressure ionization region and the lower pressure viscous flow region at the beginning of the free jet expansion. Typically, a conical skimmer with a small circular aperture is located downstream of the nozzle or capillary exit. The skimmer orifice samples a portion of the gas expanding in the free jet, effectively serving to separate the higher pressure viscous gas flow of the free jet found in the first vacuum pumping stage from subsequent vacuum pumping stages which are maintained at lower background pressure. Most mass analyzers generally operate in vacuum pressures well within the free molecular flow regime. Once ions pass through the first skimmer orifice, they may be required to pass through one or more additional pumping stages before entering the mass analyzer. Background pressures in the first pumping stage or viscous flow regime can be as high as a few torr and the background pressures usually required by mass analyzers with electron multiplier detectors fall below 1.times.10.sup.-5 torr. One exception to this mass analyzer vacuum requirement is the ion trap or three dimensional quadrupole mass spectrometer. Pressures used inside ion trap mass spectrometers can run much higher than other types of mass analyzers; however, the ion detectors still require pressures in the 10.sup.-5 torr range or better. Hence, even for ion trap mass spectrometers there is a need for efficient ion transmission from the higher viscous flow vacuum pressure region into the non-viscous flow region of the trap analyzer and ion detector.
In U.S. Pat. No. 5,157,260 a tube shaped focusing lens is described, situated inside the first pumping stage of the free jet expansion formed from gas expanding through a capillary tube from atmospheric pressure into vacuum. Gas flow between the capillary exit and the skimmer orifice as described in this patent is in the viscous flow regime, so the mean free path of molecules in this portion of the free jet molecules is quite small. The patent claims that as a result of the voltages applied to the tube lens, the ion densities near the centerline of the free jet which pass through the first skimmer orifice are enriched. U.S. Pat. No. 4,121,099 shows a conical shaped lens 70, (FIG. 7) located in the free jet expansion region between the nozzle and the first skimmer in the first pumping stage of a mass spectrometer. Voltage applied to this conical lens in the viscous flow regime of the first pumping stage of the expanding free jet helps to concentrate the ions entrained in the carrier gas closer to the center line. This enriches the ion density near the center line so that more ions can be effectively sampled through the first skimmer. It was also found that application of certain voltages to the lens elements of this viscous flow free jet region can effectively cause breaking of non-covalently bound complexes such as clusters and even covalent bonds of the ions entrained in the free jet.
Applying focusing and accelerating voltages to focusing lenses in the viscous flow region accelerates the ions along electrostatic field lines between collisions with the neutral expanding carrier gas. The net result is that the ions can be driven to follow different trajectories than the neutral carrier gas but because the mean free path between collisions is so short in this viscous flow region, the ion velocities achieved are only the local mobility limit for the local electrostatic field and gas pressure for a given ion. This mobility velocity is so slow that little translational energy in terms of electrostatic energy is imparted to the ion in the first pumping stage viscous flow regime. The repeated collisions of ions with the neutral carrier gas can, however, increase the ion's internal energy resulting in collisionally induced dissociation (CID) of that sampled ion. This effect in many cases is desirable to the user where one can reproducibly generate fragment ions by adjusting the voltage difference between the focusing and the adjacent lenses without suffering the wide range of energy spreads associated with non-viscous pressure regime CID processes used in mass spectrometric analysis. The CID technique in the free jet expansion region of an electrospray ion source is widely used and can yield important structural and identification information of molecules that are being analyzed (See, for example, Smith et. al, J. Am. Soc. Mass Spectrom., Vol. 1, p. 53, 1990). As mentioned above, the collisions in this area can also be used to decluster the solvent molecules from the analyte ions of interest which had not been effectively removed before the ion entered the free jet expansion.
The present invention describes an electrostatic lens located in the transition or slip flow pressure regime downstream of the first skimmer. This electrostatic lens aids in concentrating and focusing ions along the centerline, effectively increasing the ion transmission efficiency into the mass analyzer. This lens configuration with the appropriate applied voltages causes ion enrichment and centerline focusing of the ion beam even in a pressure region where a significant number of collisions with the neutral carrier gas are still occurring. In addition, the lensing system allows for increased ion transmission independent of the operational voltages of the lenses in the viscous flow pressure region where the degree of CID and declustering processes can be adjusted separately. The free flight relative electrostatic energy of the ion being focused in vacuum is not established until the gas pressure of neutral background gas is decreased to the molecular flow region. In the molecular flow vacuum region ions can be accelerated by electrostatic forces with negligible loss of translational energy from collisions with background gas. The present invention addresses a lens configuration which focuses ions in the transition or slip flow pressure region after the viscous flow region and before or as they enter the free molecular flow region. Voltage settings can then be applied to maximize ion transmission and collimate the ion beam through this vacuum regime where collisions with background neutral gas still occur. The invention described is particularly useful for multiple pumping stage systems with progressively lower pressure per vacuum stage. The ion beam is focused and the ion energy is set just after the transition pressure region between viscous flow and free molecular flow vacuum regions resulting in an overall increase in ion transmission efficiency from an atmospheric pressure ion source into a mass analyzer. The use of multiple pumping stages can increase overall system sensitivity at lower cost. Removing more gas on a mass basis at higher pressures allows greater throughput for less cost than trying to remove the same gas mass loading at lower pressures with larger vacuum pumps. For example, it is more cost effective to remove gas with rotary pumps than with diffusion, turbomolecular, or cryopumps. Multiple staged pumping systems allow the removal of much gas with rotary pumps in the first and even the second vacuum stage effectively reducing the gas load on the lower pressure vacuum stages. Critical to the performance of such staged vacuum pumping systems is the efficiency in ion transmission from the viscous to free molecular flow region where the ions can be electrostatically focused and accelerated with little effect from collisions with neutral background gas.